In a well-known technique for separating or analyzing samples to be investigated, a capillary array is constructed by combining a plurality of capillaries, and then the samples to be analyzed or separated are supplied to each capillary together with an electrophoresis medium. Samples supplied to the capillaries include DNA labeled with a fluorescent substance and proteins. Such a technique is described in U.S. Pat. Nos. 5,366,608, 5,529,679, 5,516,409, 5,730,850, 5,790,729, 5,582,705, 5,439,578, and 5,274,240, for example. From the viewpoint of separation or analysis throughput, use of multiple capillaries can provide more advantages than the electrophoresis method using a slab gel.
A multicapillary array electrophoretic device includes a casing housing a constant-temperature bath for storing the capillary array in a constant temperature environment, a gel pump unit for replacing a gel polymer as a separating medium in the capillary array, an irradiation/detection unit for irradiating the capillary array with laser light or the like to detect fluorescence from fluorescence-labeled samples, and an autosampler for continuously measuring many samples, for example. An electrode is formed on one end (sample loading end) of the capillary array to which a negative voltage can be applied. When DNA is injected into the capillaries, the autosampler is moved so that the negative electrode is submerged in a solution mounted on the autosampler that contains samples, and then a voltage is applied. When electrophoresis of the injected samples is carried out, the negative electrode is submerged in a buffer solution mounted on the autosampler, and then a voltage is applied. The DNA samples and the buffer solution are mounted on a tray on the autosampler. The samples are often put in a general-purpose microtiter plate capable of storing many samples at once, which is then combined with a dedicated adapter or the like and mounted on the tray. The buffer solution is put in a buffer reservoir intended for that purpose which is mounted on the tray. The microtiter plate and the buffer reservoir are covered with septa for preventing the evaporation of the samples. The septa are provided with slits for allowing the insertion of capillaries.
The microtiter plate and the buffer reservoir are thus simply placed on the tray of the autosampler such that they are fixed in X and Y directions but not in Z direction. As a result, when the autosampler is moved downward and the sample loading end of the capillary array is removed from the wells in the microtiter plate or the buffer reservoir, the microtiter plate or the buffer reservoir could be lifted by the capillary array due to the friction between the array and the septa.
In order to prevent this, conventionally a press-down plate (to be hereafter referred to as a “stripper plate”) is used. The stripper plate can be moved up and down along the sample loading end of the capillary array. For example, when a sample is introduced into the capillary array, the autosampler is initially moved in X and Y directions so as to position a target well directly below the capillary array where the sample loading end of the capillary array can be inserted into the well in the microtiter plate containing the sample. The autosampler is then moved upwards, when the stripper plate comes into contact with the autosampler and is lifted. The stripper plate exerts a force pushing the microtiter plate downward provided by a spring secured to the stripper plate or by its own weight. Thus, when the autosampler is moved downward, the microtiter plate is pressed against the tray on the autosampler until the capillary array is completely pulled out, thus preventing the lifting of the microtiter plate.
However, this technique using the stripper plate has several problems. During sample introduction or electrophoresis, for example, a downward force is exerted on the autosampler as long as the stripper plate is in contact with the autosampler. The autosampler is driven by a stepping motor, for example. Therefore, the autosampler is prevented from dropping by the static torque provided by the stepping motor as long as it is energized. When the motor is not energized, however, there is the danger of the autosampler being dropped due to the force provided by the stripper plate. For example, when the power to the device is turned off and the device is placed in a standby mode, it is necessary to keep the sample loading end of the capillary array submerged in the buffer reservoir or a water reservoir so as to prevent the drying of the capillary array attached to the device. However, as the stepping motor is not energized in this mode, the autosampler could be dropped as it is pushed by the stripper plate. A similar problem could occur when the door of the device is opened by the operator during electrophoresis or while the autosampler is moving, because opening of the door requires all the operations to be automatically stopped and various power supplies to be shut down. It is of course possible to design the device such that the autosampler would not be dropped unless it is pushed down with a force sufficiently greater than the stripper plate. This, however, would greatly inconvenience the maintenance or servicing operations where the autosampler would have to be moved manually.
Further, during sample introduction or electrophoresis, a high voltage of the order of several to several tens of kV is applied to the sample introduction end of the capillary array. As a result, there is the danger of discharge from the array electrode portion to the device chassis via the stripper plate.
These problems become increasingly pronounced as the number of capillaries in the capillary array increases, thus posing a major obstacle in increasing the throughput of the device.
Further, while the capillary array in its entirety is retained in the constant temperature bath for maintaining the array at a certain temperature, the sample loading end must be exposed outside the bath. The presence of a stripper plate makes it necessary to increase the length of the capillary portions that are outside the constant temperature bath, thereby adversely affecting the performance of electrophoresis.
It is therefore an object of the invention to provide a capillary array electrophoretic device capable of automatic operation without the use of a stripper plate.